Inflammatory Biomarkers: A Horse’s Early Warning System?: Paulick Report 3/17/16

By: Natalie Voss

Veterinarians have long been searching for some sort of advance warning that a horse may be on the brink of suffering a serious bone or soft tissue injury. Recent research into biomarkers may provide practitioners with more tools to anticipate problems or a better understanding of a horse’s discomfort after it has begun.

According to a definition established by a working group of researchers in 2011, a biomarker is a measurable characteristic that’s indicative of a normal biological process, a response to drugs, or a response to a pathogen. Biomarkers may be found in blood or urine. Some biomarkers have a unique composition that demonstrates which part of the body they come from, such a specific organ. Others can signal the presence of inflammation but do not reveal its location.

Dr. Agnieszka Turlo, doctoral student at the Warsaw University of Life Sciences, said veterinarians are already finding ways that biomarkers can help them diagnose a patient in the field.

“The perfect example is Serum Amyloid A (SAA), a protein released to the blood from the liber in the early phase of inflammation known as acute phase response,” said Turlo, who noted that SAA concentration can increase 1,000-fold as a reaction to certain types of tissue damage. “Analysis of SAA blood level may be helpful in evaluation of the severity of disease, setting prognosis (especially in colic cases and in horses recovering after surgery) and monitoring the efficacy of therapy.”

SAA has proven so useful to help practitioners learn about organ-based inflammation that it is now sometimes featured on basic blood tests alongside other common parameters like liver enzymes.

Since it’s become a useful tool in the world of organ inflammation, some researchers wondered whether SAA could provide information about athletic injuries. A study released in October in the open-access journal Plos One presented data from researchers at the Warsaw University of Life Sciences that suggests that it can. The authors were curious whether biomarkers would appear differently in the blood based on the source tissue of a horse’s injury, so they tested blood from 56 Thoroughbreds — 28 with injuries, 28 without. Their work found that SAA was elevated for four days after injury in horses with soft tissue damage, but healthy horses and those with bone-related stress injuries did not experience this change.

The significance behind the work is limited because of the study’s small size, cautioned Turlo, who was one of the study’s co-authors. It’s still too early to know whether SAA will prove adequately specific in diagnosis of inflammation to avoid costly procedures like MRIs or bone scans. Nonspecific biomarkers (those that don’t clearly identify their source) are also trickier to pin down because they could be circulating due to something as serious as a festering ligament strain or something as simple as a recent vaccination. More research is needed before biomarkers can be considered a reliable diagnostic tool.

One area in which biomarker measurement could be helpful, however, is injury prediction. The University of California-Davis has established that most fatal bone fractures in racehorses (85 percent) occur in areas with preexisting stress pathology. Scientists believe that soft tissue injuries also take place as the result of chronic stress and long-term failure of the tissue, rather than as sudden and seemingly random events.

“Due to its increasing popularity in equine practice, it is important to recognize as many conditions leading to the increase in blood SAA as possible, especially in cases when no obvious clinical signs of disease or injury are present,” said Turlo. “In such cases, increased SAA may suggest that the horse should not be pushed in training and that close monitoring of its health and fitness is needed.”

Dr. David Horohov, equine immunology researcher at the Gluck Equine Research Center in Lexington, Ky., has been working to draw a connection between biomarkers in racehorses and injury risk. Although he is encouraged by his results so far, Horohov said it’s challenging to establish an association between the two; injuries are, statistically speaking, uncommon occurrences, which means scientists need to study large populations of horses in order to see a few injuries, and they need a large number of injuries to draw conclusions. In his most recent study, trainers of horses with high amounts of inflammatory biomarkers reduced the horses’ workload after learning their test results, and the horses did not experience injury — which was great news for the horses, but tricky for the researchers, as it prevented them from seeing how the horses might have fared without intervention.

“Because we don’t have that data to say for certain, I tend to emphasize more that this is a method that we use to ensure that your horse is training within its capabilities,” said Horohov. “As long as it doesn’t produce inflammatory mediators in response to the exercise you’re giving it, you’re staying within its capabilities.”

The next step for Horohov and his team is measuring biomarker levels in horses suffering soft tissue injuries during races, and comparing those with horses who are pulled up or vanned off, but found not to have serious soft tissue injuries. He suspects that horses with elevated biomarker levels at the time of injury may have come into their races with elevated levels, but it’s too early to say for sure.

In the meantime, work by Horohov’s laboratory is making headlines. A trio of students at the University of Kentucky — Julia Fabiani, Stefanie Pagano, and Ben Martin — have created a business plan to market the testing process used in the laboratory to look for biomarkers. The project, titled Race Assured, was originally an academic assignment that won a number of student business competitions, but Horohov said it’s drawn real-world interest from both Central Kentucky veterinarians and international experts willing to participate in the project.

“It’s all a student exercise but they’re very serious about it,” he said. “It’s somewhat gratifying that there’s as much interest as there is. It’s an area that strikes a tone not just with people in the industry, but with people outside the industry. They’re not talking necessarily with people who have an interest in racing, but with people who can identify with the need for early diagnostics.”